Abstract CT070: Double-blind placebo-controlled trial of AL102 for treatment of progressing desmoid tumors: the RINGSIDE phase 3 study design
Authors: Mrinal Gounder, Robin L. Jones, Jonathan Yovell, Gary Gordon, Bernd Kasper
Journal: Cancer Research (2023)

Abstract Background: There is an unmet need for effective systemic therapy for desmoid tumors (DT, aggressive fibromatosis) that provides durable tolerability, symptom improvement, and tumor regression. Gamma secretase inhibitors (GSIs) demonstrate antitumor activity against DT. AL102 is a potent, orally available, selective GSI under investigation as an antineoplastic agent. Methods: RINGSIDE (AL-DES-01) is a 2-part Phase 2/3 study. In the open-label Phase 2 study (Part A), adults with progressing DT (≥10% unidimensional growth within 18 months or DT-related pain requiring non-opioid medication) were randomized to three dosing regimens: 1.2 mg once daily, 2 mg intermittent BIW (2 days on 5 days off), or 4 mg intermittent BIW. RINGSIDE Phase 3 (Part B) is a double-blind, placebo-controlled study evaluating the chosen dose regimen from Phase 2 (1.2 mg once daily) in adults and adolescents (≥12 years of age) with recurrent or treatment-naïve histologically confirmed progressing DT per investigator. For eligibility, progression is defined as ≥20% measured by MRI or CT scan according to RECIST v1.1 within 12 months of the screening visit. Planned enrollment is for ≈156 subjects globally to be randomized 1:1 to either AL102 1.2 mg once daily or placebo. Randomization will be stratified according to tumor location: intra-abdominal vs. extra-abdominal (including abdominal wall). Subjects will undergo MRI or CT scans (using the same modality throughout the study) every 12 weeks to assess tumor response according to RECIST v1.1 by blinded independent central review (BICR). The primary endpoint is progression-free survival (PFS) by BICR based on RECIST v1.1. Primary and secondary endpoints are summarized in Table 1. The trial is currently enrolling. Table 1. RINGSIDE Phase 3 Study Endpoints Objectives Endpoints Primary Evaluate effects of AL102 on disease progression PFS defined as time from randomization until date of assessment of progression (assessed by BICR based on RECIST v1.1) or death by any cause Secondary Evaluate additional effects of AL102 on tumor response • ORR (CR and PR) by BICR based on RECIST v1.1 • DOR defined by time from CR or PR (by BICR based on RECIST v1.1) until first documentation of disease progression or death from any cause Evaluate effects of AL102 on quality of life • Change from baseline in quality of life as determined by: • GOunder/Desmoid Tumor Research Foundation (DTRF) DEsmoid Symptom Scale and Impact Scale (GODDESS) • Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function • EuroQol 5-Dimensional (EQ-5D-3L) questionnaire • Patient’s Global Impression of Change (PGI-C) • Change from baseline in pain assessment using Brief Pain Inventory (BPI) short form Evaluate safety and tolerability of AL102 • Frequency, duration and severity of treatment-emergent adverse events (TEAEs) and serious AEs • Time to treatment discontinuation due to TEAE BICR: blinded independent central review; CR: complete response; DOR: duration of response; ORR: objective response rate; PR: partial response; PFS: progression-free survival; RECIST: Response Evaluation Criteria in Solid Tumors Citation Format: Mrinal Gounder, Robin L. Jones, Jonathan Yovell, Gary Gordon, Bernd Kasper. Double-blind placebo-controlled trial of AL102 for treatment of progressing desmoid tumors: the RINGSIDE phase 3 study design [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT070.